The G Protein β Subunit Is a Determinant in the Coupling of Gs to the β1-Adrenergic and A2a Adenosine Receptors*
By W. McIntire, G. MacCleery, J. Garrison. Journal of Biological Chemistry, 2001
96 citations recorded by the source corpus.
The signaling specificity of five purified G protein βγ dimers, β1γ2, β2γ2, β3γ2, β4γ2, and β5γ2, was explored by reconstituting them with Gs α and receptors or effectors in the adenylyl cyclase cascade. The ability of the five βγ dimers to support receptor-α-βγ interactions was examined using membranes expressing the β1-adrenergic or A2a adenosine receptors. These receptors discriminated among the defined heterotrimers based solely on the β isoform. The β4γ2 dimer demonstrated the highest coupling efficiency to either receptor. The β5γ2 dimer coupled poorly to each receptor, with EC50 values 40–200-fold higher than those observed with β4γ2. Strikingly, whereas the EC50 of the β1γ2 dimer at the β1-adrenergic receptor was similar to β4γ2, its EC50 was 20-fold higher at the A2a adenosine receptor. Inhibition of adenylyl cyclase type I (AC1) and stimulation of type II (AC2) by the βγ dimers were measured. βγ dimers containing Gβ1–4 were able to stimulate AC2 similarly, and β5γ2 was much less potent. β1γ2, β2γ2, and β4γ2inhibited AC1 equally; β3γ2 was 10-fold less effective, and β5γ2 had no effect. These data argue that the β isoform in the βγ dimer can determine the specificity of signaling at both receptors and effectors.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/b3962ad1f74fe98d6370d5cac8ecb526c12e3a7c
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Citations in the corpus
- Heterotrimeric G protein activation by G-protein-coupled receptors (2008, background): “Interestingly, although Gβ 1 had a similar potency to Gβ 4 in coupling to the β 1 -adrenergic receptor, its potency was 20-fold lower when coupling to the adenosine recepto”
- International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. (2001, unknown): “A2A receptors vary in their affinity for Gs proteins containing various types of -subunits and interact most avidly with G proteins containing 4 (McIntire et al., 2001).”